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Background: Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. Methods: MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. Results: Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. Conclusion: Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Endostar, a novel modified recombinant human endostatin, is now widely studied for the treatment of diseases that are characterized or caused by pathological angiogenesis. However, its molecular mechanism remains unclear. In this study, we investigated the effects of Endostar on the Wnt/β-catenin signaling pathway, which has emerged as an important aspect of angiogenesis. We showed that Endostar significantly inhibited the proliferation, migration, invasion, and capillary-like tube formation of human umbilical vascular endothelial cells in a dose-dependent manner. Using a luciferase reporter assay, we also demonstrated that Endostar suppressed β-catenin-dependent T cell factor transcriptional activity in increasing doses. Moreover, we found that Endostar treatment also restricted the stabilized mutant β-catenin-mediated increase in transcriptional activity, suggesting that Endostar exerts its inhibitory influence on Wnt/β-catenin signaling by targeting β-catenin or its downstream molecules. Western blot and immunofluorescence results revealed that Endostar significantly decreased nuclear and total β-catenin levels. Finally, we discovered that Endostar down-regulated cyclin D1 and VEGF, two proteins that are known as the downstream targets of Wnt/β-catenin signaling and that also play important roles in angiogenesis. Our findings suggested that Endostar inhibits angiogenesis and that the downregulation of the Wnt/β-catenin signaling pathway may be involved in the inhibition of angiogenesis by Endostar. These results support the use of Endostar in further clinical applications. [ABSTRACT FROM AUTHOR]

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications. [Display omitted] [ABSTRACT FROM AUTHOR]